Lignin-assisted construction of sub-10 nm supramolecular self-assembly for photothermal immunotherapy and potentiating anti-PD-1 therapy against primary and distant breast tumors

Photothermal therapy(PTT)has brought hope for cancer treatments,with hyperthermia-induced immunogenic cell death(ICD),which is a critical part of therapeutically induced antitumor immune responses.Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation,therefore demonstrating urgent requirements for ICD amplifier.Herein,a sub-10 nm supramolecular nanoassembly was formed by coassembly of clinically approved aluminum adjuvant and commonly used indocyanine green(ICG)under the assistance of lignosulfonate(LS,a green and sustainable multifunctional lignin derivative)for localized photothermal-immunotherapy of breast cancer.The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD,efficiently eliciting solid immune responses through dendritic cells(DCs)activation and cytotoxic T-cell responses initiation for tumor killing.Moreover,anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity.The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy,which shows promise for delivering other therapeutics in biomedical applications.

Composite electrolyte with self-inserted structure and all-trans F conformation provides fast Li^(+)transport for solid-state Li metal batteries

Solid-state Li metal battery has attracted increasing interests for its potentiallyhigh energy density and excellent safety assurance, which is a promising candidatefor next generation battery system. However, the low ionic conductivityand Li^(+) transport number of solid-state polymer electrolytes limit their practicalapplication. Herein, a composite polymer electrolyte with self-insertedstructure is proposed using the layered double hydroxides (LDHs) as dopant toachieve a fast Li^(+) transport channel in poly(vinylidene-co-trifluoroethylene) [P(VDF-TrFE)] based polymer electrolyte. In such a composite electrolyte, P(VDF-TrFE) polymer has an all-trans conformation, in which all fluorineatoms locate on one side of the polymer chain, providing fast Li^(+) transporthighways. Meanwhile, the LDH can immobilize the anions of Li salts based onthe electrostatic interactions, promoting the dissociation of Li salts, therebyenhancing the ionic conductivity (6.4 × 10^(-4) S cm^(-1)) and Li^(+) transferencenumber (0.76). The anion immobilization effect can realize uniform electricfield distribution at the anode surface and suppress the dendritic Li growth.Moreover, the hydrogen bonding interaction between LDH and polymerchains also endows the composite electrolyte with strong mechanical properties.Thus, at room temperature, the Li jj Li symmetric cells can be stablycycled over 1000 h at a current density of 0.2 mA cm^(-2), and the full cells withLiFePO_(4) cathode deliver a high capacity retention (>95%) after 200 cycles. This work offers a promising route to construct solid-state polymer electrolytes withfast Li^(+) transport.

Cooperative coordination-mediated multi-component self-assembly of“all-in-one”nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation,high drug-loading efficiency,and excellent therapeutic efficacy.Herein,MnAs-ICG nanospike was generated by self-assembly of indocyanine green(ICG),manganese ions(Mn^(2+)),and arsenate(AsO_(4)^(3−))based on electrostatic and coordination interactions,effectively integrating the bimodal imaging ability of magnetic resonance imaging(MRI)and fluorescence(FL)imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an“all-in-one”theranostic nano-platform.The as-prepared MnAs-ICG nanospike had a uniform size,well-defined nanospike morphology,and impressive loading capacities.The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability,enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components.In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect,prolonged blood circulation and increased tumor accumulation compared to their individual components,effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect.Taken together,this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

An engineered xCas12i with high activity,high specificity,and broad PAM range

Dear Editor,The clustered regularly interspaced short palindromic repeats-Cas(CRISPR-Cas)systems,including type II Cas9 and type V Cas12 systems,which serve in the adaptive immunity of prokaryotes against viruses,have been developed into genome-editing tools(Anzalone et al.,2020;Doudna,2020).Compared with type II systems,the type V systems including V-A to V-K showed more functional diversity(Yan et al.,2019).Amongst them,Cas12i has a relatively smaller size(1,033-1,093 aa),compared to SpCas9 and Cas12a,and has a 5'-TTN protospacer adjacent motif(PAM)preference(Yan et al.,2019).

Influence of Surface Nanocrystallization on Ti Ion Implantation of Pure Iron

In order to increase the depth or concentration of Ti ion implantation of pure iron, the surface mechanical attrition treatment(SMAT), which can fabricate a nanometer-grained surface layer without porosity and contamination in a pure iron plate, was used before ion implantation. Ti ion was implanted into the SMA treated sample and coarse-grained counterpart by using a metal vapor vacuum arc source implanter. The changing of depth and concentration of Ti was studied in a function of implantation time.By optical microscopy, transmission electron microscopy and X-ray diffraction, the grain size of the nano structured surface was studied. Micro-hardness, friction and wear behavior of nano surface layers were studied. By energy dispersive X-ray spectroscopy and Auger electron spectroscopy, the chemical composition and concentration of Ti ion in the surface implantation layer were studied. Experimental results showed that the concentration of Ti increased dramatically compared with untreated coarsegrained samples, which is attributed to the existence of higher density of defects(supersaturated vacancies, dislocations, non-equilibrium grain boundaries etc.) and compression stress field in the SMA treated nanocrystallined surface layer. The interaction between the defects and the implanted solute atoms leads to the increment of solid solubility. But the implantation depth showed inconspicuous change. It is shown that the ion range is just relevant to the energy and mass of the ion, dose of injection,the mass and density of target material.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

Approximately 140 million people worldwide are homozygous carriers of APOE4(ε4),a strong genetic risk factor for late onset familial and sporadic Alzheimer’s disease(AD),91%of whom will develop AD at earlier age than heterozygous carriers and noncarriers.Susceptibility to AD could be reduced by targeted editing of APOE4,but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies.Here,we first screened eight cytosine base editor variants at four injection stages(from 1-to 8-cell stage),and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate(up to 100%)with the lowest bystander effects.In particular,80%of AD-susceptibleε4 allele copies were converted to the AD-neutralε3 allele in humanε4-carrying embryos.Stringent control measures combined with targeted deep sequencing,whole genome sequencing,and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells.Furthermore,base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage.Finally,we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia.Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos,a potential approach for reducing human susceptibility to AD or other genetic diseases.

Leap of Li Metal Anodes from Coin Cells to Pouch Cells:Challenges and Progress

Li metal anodes have attracted tremendous attention in the last decade because of their high theoretical capacities and low electrochemical potentials.However,until now,there has only been limited success in improving the interfacial and structural stabilities and in realizing the highly controllable and large-scale fabrication of this emerging material;these limitations have posed great obstacles to further performing fundamental and applied studies in Li metal anodes.In this review,we focus on summarizing the existing challenges of Li metal anodes based on the leap from coin cells to pouch cells and on outlining typical methods for designing Li metal anodes on demand;we controllably engineer their surface protection layers and structure sizes by encapsulating structured Li metal inside a variety of synthetic protection layers.We aim to provide a comprehensive understanding and serve as a strategic guide for designing and fabricating practicable Li metal anodes for use in pouch batteries.Challenges and opportunities regarding this burgeoning field are critically evaluated at the end of this review.